Synthesis of alpha-galactosyl ceramide (KRN7000) and analogues thereof via a common precursor and their preliminary biological assessment.
A new practical synthesis of alpha-GalCer and of its analogues is presented, opening the chance to easily modify the sphingosine chain. The common precursor is a disaccharide, obtained by coupling tetra-O-benzyl-D-galactose with allyl 2,3-O-isopropylidene-D-lyxofuranoside. Introduction of alkyl chains via Wittig reaction (for alpha-GalCer and OCH) or via Williamson reaction (for oxa analogues) followed by standard synthetic steps allows one to efficiently obtain such compounds. The analogues are able to activate iNKT cells when presented by CD1d expressing cells.
Michieletti
Mario
M
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale Amedeo Avogadro, via Bovio 6, 28100 Novara, Italy.
Bracci
Antonio
A
Compostella
Federica
F
De Libero
Gennaro
G
Mori
Lucia
L
Fallarini
Silvia
S
Lombardi
Grazia
G
Panza
Luigi
L
D004187:Disaccharides / Q000737:chemistry; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007376:Interleukin-2 / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism; D013110:Sphingosine / Q000737:chemistry
D004187:Disaccharides; D005699:Galactosylceramides; D007376:Interleukin-2; D013110:Sphingosine; C103873:KRN 7000